339 research outputs found

    Multidimensional Scaling of Varietal Data in Sedimentary Provenance Analysis

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    Varietal studies of sedimentary provenance use the properties of individual minerals or mineral groups. These are recorded as lists of numerical tables that can be difficult to interpret. Multidimensional Scaling (MDS) is a popular multivariate ordination technique for analyzing other types of provenance data based on, for example, detrital geochronology or petrography. Applying MDS to varietal data would allow them to be treated on an equal footing with those other provenance proxies. MDS requires a method to quantify the dissimilarity between two samples. This paper introduces three ways to do so. The first method (“treatment-by-row”) turns lists of (compositional) data tables into lists of vectors, using principal component analysis. These lists of vectors can then be treated as “distributional” data and subjected to MDS analysis using dissimilarity measures such as the Kolmogorov-Smirnov statistic. The second method (“treatment-by-column”) turns lists of compositional data tables into multiple lists of vectors, each representing a single component of the varietal data. These multiple distributional data sets are subsequently subjected to Procrustes analysis or 3-way MDS. The third method uses the Wasserstein-2 distance to jointly compare the rows and columns of varietal data. This arguably makes the best use of the data but acts more like a “black box” than the other two methods. Applying the three methods to a detrital titanite data set from Colombia yields similar results. After converting varietal data to dissimilarity matrices, they can be combined with other types of provenance data, again using Procrustes analysis or 3-way MDS

    The INCLUDE study: INtegrating and improving Care for patients with infLammatory rheUmatological DisordErs in the community; identifying multimorbidity: Protocol for a pilot randomized controlled trial.

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    Background: Patients with inflammatory rheumatic conditions such as rheumatoid arthritis, polymyalgia rheumatica and ankylosing spondylitis are at increased risk of common comorbidities such as cardiovascular disease, osteoporosis and anxiety and depression which lead to increased morbidity and mortality. These associated morbidities are often un-recognized and under-treated. While patients with other long-term conditions such as diabetes are invited for routine reviews in primary care, which may include identification and management of co-morbidities, at present this does not occur for patients with inflammatory conditions, and thus, opportunities to diagnose and optimally manage these comorbidities are missed. Objective: To evaluate the feasibility and acceptability of a nurse-led integrated care review (the INtegrating and improving Care for patients with infLammatory rheUmatological DisordErs in the community (INCLUDE) review) for people with inflammatory rheumatological conditions in primary care. Design: A pilot cluster randomized controlled trial will be undertaken to test the feasibility and acceptability of a nurse-led integrated primary care review for identification, assessment and initial management of common comorbidities including cardiovascular disease, osteoporosis and anxiety and depression. A process evaluation will be undertaken using a mixed methods approach including participant self-reported questionnaires, a medical record review, an INCLUDE EMIS template, intervention fidelity checking using audio-recordings of the INCLUDE review consultation and qualitative interviews with patient participants, study nurses and study general practitioners (GPs). Discussion: Success of the pilot study will be measured against the engagement, recruitment and study retention rates of both general practices and participants. Acceptability of the INCLUDE review to patients and practitioners and treatment fidelity will be explored using a parallel process evaluation. Trial Registration: ISRCTN12765345

    Quantitative principles of cis-translational control by general mRNA sequence features in eukaryotes.

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    BackgroundGeneral translational cis-elements are present in the mRNAs of all genes and affect the recruitment, assembly, and progress of preinitiation complexes and the ribosome under many physiological states. These elements include mRNA folding, upstream open reading frames, specific nucleotides flanking the initiating AUG codon, protein coding sequence length, and codon usage. The quantitative contributions of these sequence features and how and why they coordinate to control translation rates are not well understood.ResultsHere, we show that these sequence features specify 42-81% of the variance in translation rates in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Arabidopsis thaliana, Mus musculus, and Homo sapiens. We establish that control by RNA secondary structure is chiefly mediated by highly folded 25-60 nucleotide segments within mRNA 5' regions, that changes in tri-nucleotide frequencies between highly and poorly translated 5' regions are correlated between all species, and that control by distinct biochemical processes is extensively correlated as is regulation by a single process acting in different parts of the same mRNA.ConclusionsOur work shows that general features control a much larger fraction of the variance in translation rates than previously realized. We provide a more detailed and accurate understanding of the aspects of RNA structure that directs translation in diverse eukaryotes. In addition, we note that the strongly correlated regulation between and within cis-control features will cause more even densities of translational complexes along each mRNA and therefore more efficient use of the translation machinery by the cell

    Assessing Deaf Cultural Competency of Physicians and Medical Students

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    The Medical Students, Cancer Control, and the Deaf Community Training program (DCT) intended to create physicians who were culturally competent to care for deaf patients were evaluated. DCT medical students (n = 22), UCSD medical faculty (n = 131), and non-DCT medical students (n = 211) were anonymously surveyed about their perceptions related to deaf patients, deaf cultural competency, and interpreter use. The faculty and non-DCT medical students displayed less knowledge than the DCT students. These findings suggest that training medical students in deaf cultural competency can significantly increase their capacity to care for community members and reduce the health disparities experienced by this community

    Variation in Uteroglobin-Related Protein 1 (UGRP1) gene is associated with Allergic Rhinitis in Singapore Chinese

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    <p>Abstract</p> <p>Background</p> <p>Uteroglobin-Related Protein 1 (<it>UGRP1</it>) is a secretoglobulin protein which has been suggested to play a role in lung inflammation and allergic diseases. UGRP1 has also been shown to be an important pneumoprotein, with diagnostic potential as a biomarker of lung damage. Previous genetic studies evaluating the association between variations on <it>UGRP1 </it>and allergic phenotypes have yielded mixed results. The aim of this present study was to identify genetic polymorphisms in <it>UGRP1 </it>and investigate if they were associated with asthma and allergic rhinitis in the Singapore Chinese population.</p> <p>Methods</p> <p>Resequencing of the <it>UGRP1 </it>gene was conducted on 40 randomly selected individuals from Singapore of ethnic Chinese origin. The polymorphisms identified were then tagged and genotyped in a population of 1893 Singapore Chinese individuals. Genetic associations were evaluated in this population comparing 795 individuals with allergic rhinitis, 718 with asthma (of which 337 had both asthma and allergic rhinitis) and 717 healthy controls with no history of allergy or allergic diseases.</p> <p>Results</p> <p>By resequencing the <it>UGRP1 </it>gene within our population, we identified 11 novel and 16 known single nucleotide polymorphisms (SNPs). TagSNPs were then genotyped, revealing a significant association between rs7726552 and allergic rhinitis (Odds Ratio: 0.81, 95% Confidence Interval: 0.66-0.98, P = 0.039). This association remained statistically significant when it was analyzed genotypically or when stratified according to haplotypes. When variations on <it>UGRP1 </it>were evaluated against asthma, no association was observed.</p> <p>Conclusion</p> <p>This study documents the association between polymorphisms in <it>UGRP1 </it>and allergic rhinitis, suggesting a potential role in its pathogenesis.</p

    HIT family genes: FHIT but not PKCI-1/HINT produces altered transcripts in colorectal cancer

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    Forty-five colorectal adenocarcinomas were examined for alterations in the HIT family genes FHIT and PKCI-1/HINT by a combination of reverse transcriptase polymerase chain reaction and DNA sequencing. In all cases a single transcript corresponding to the reported sequence was detected using primers specific for the PKCI-1/HINT gene. In contrast multiple transcripts were detected using primers specific for the FHIT gene transcript. 6% (3/45) of tumours evinced no detectable expression of any FHIT transcript and a further 12% (6/45) produced only the normal full length transcripts. Ninety-six aberrant transcripts were characterized from the remaining tumours. Deviations from the normal full length sequence characterized included deletions, insertions of novel sequences, a point mutation as well as the usage of a putative alternate splice site in exon 10. Message variants were detected with approximately equal frequency in all tumour stages with the exception that templates with insertions were found solely in Dukes’ stage B tumours (P < 0.001). With the exception of the putative alternate splice site, aberrant transcripts were not detected in matched normal mucosa. These results suggest that members of the HIT family of genes are only selectively involved in tumorigenesis and that perturbation of FHIT gene expression is an early event in colorectal tumorigenesis. © 1999 Cancer Research Campaig

    HSV Usurps Eukaryotic Initiation Factor 3 Subunit M for Viral Protein Translation: Novel Prevention Target

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    Prevention of genital herpes is a global health priority. B5, a recently identified ubiquitous human protein, was proposed as a candidate HSV entry receptor. The current studies explored its role in HSV infection. Viral plaque formation was reduced by ∼90% in human cells transfected with small interfering RNA targeting B5 or nectin-1, an established entry receptor. However, the mechanisms were distinct. Silencing of nectin-1 prevented intracellular delivery of viral capsids, nuclear transport of a viral tegument protein, and release of calcium stores required for entry. In contrast, B5 silencing had no effect on these markers of entry, but inhibited viral protein translation. Specifically, viral immediate early genes, ICP0 and ICP4, were transcribed, polyadenylated and transported from the nucleus to the cytoplasm, but the viral transcripts did not associate with ribosomes or polysomes in B5-silenced cells. In contrast, immediate early gene viral transcripts were detected in polysome fractions isolated from control cells. These findings are consistent with sequencing studies demonstrating that B5 is eukaryotic initiation factor 3 subunit m (eIF3m). Although B5 silencing altered the polysome profile of cells, silencing had little effect on cellular RNA or protein expression and was not cytotoxic, suggesting that this subunit is not essential for host cellular protein synthesis. Together these results demonstrate that B5 plays a major role in the initiation of HSV protein translation and could provide a novel target for strategies to prevent primary and recurrent herpetic disease
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